Rheumatoid arthritis/ autoimmunity
What is rheumatoid arthritis?
“arthro” – joint, “itis" – inflammation Risk factors
Autoimmune disease – inflammation Environmental
and destruction -Smoking
Commonest inflammatory joint -Obesity
disease – 1% population Genetic
Age of onset commonly 3rd to 6th -HLA DR4+
decade Immune response
3 times more prevalent in females -RF / anti-CCP positive (hallmark)
7 million sufferers by 2030 Moderate alcohol consumption may be beneficial in
Its symmetrical, if you have preventing onset –anti-inflammatory
defamation in one hand, you’re likely Excessive consumption – gout – inflammatory arthritis
to see the same in the other hand
All immune cells start as Haematopoietetic stem cells
These differentiate to become myeloid or lymphoid cells
IF goes down the Myeloid route typically innate immune system.
Innate immune system, is the first line of deffence, system responds the same way to each challenge it
encounters, responsiple for red blood cell and platlet production
More importantly prdocues: neutrophil, monocytes- macrophages and dendritic cells
Neutrophils and macrophages are phagocytes, so will engulf pathogens, removes debris and aim to restore
homeostasis
Dendritic cells are antigen presenting cells, so will take components from either the body, or outside the
body and will present them on their surface and provides the link to the adaptive immune system.
The dendritic cells present to T cells and B cells, which are produced by lymphoid progenitors
B cells produce antibpodies, t cells carry out effective functions: CD4= helper T cells (communicate with
other components of the immune system, so the components know when to activate, where to go ect),
CD8= cytotoxic T cells, which kill pathogens ( CD8 don’t play a huge role in rheumatoid arthritis)
, Diagnosis Rheumatoid factor (RF)
Antibodies that are raised against the crystalised fragments of
Joint Involvement- how many IgG (IgG is the most common form of antibody in the body in
are affected, sre they large general)
joints/ small joints Rheumatoid factors recognise the Anti-Fc region of IgG
Serology- positive for So you are producing antibodies in your body against IgG,
antibodies, such as rheumatoid which is problematic due to the prevalence of IgG in the body
factors and anti- CCP (one of The RF can be any class of antibodies: (in order of most
the main ways for diagnosis- if prevalent form: IgM > IgG > IgA > IgD > IgE
you have these antibodies it is So IgM and IgG are the main activators of the complement
likely RA) system contributes to the inflammatory affect
Acute phase reactants- proteins 80-85% of patients with RA become RF positive within 2
that are largely produced by years. so you can be RF negative for several months of having
liver, which are upregulated RA
with rheumatoid arthritis High titres of RF correlate with poor prognosis, so high levels
Duration- how long you’ve of RF= more likely for RA to be severe and progress faster
suffered with it Activation of complement system
Anti-cyclic citrullinated peptide (ANTI-CCP)
IgG antibody, which is produced against
synovial membrane peptides
These peptides are not normally exposed
However, when the joint starts to become
damaged, these peptides become exposed and
there is a change in arginine to a citrulline
These modified peptides are seen as foreign to
the body body acts against it
Only about 65% of RA patients have Anti-
CCP, but 95% of those with anti-CCP have RA
Diagnostic (because of the specificity(95%)
and prognostic, as high titres correlate with
disease severity
In RA: inflammation, destruction and
expansion of synovium
Granulocytes produce PAD
Action of PAD enzyme: converts arginine into
citrulline, so the modified peptide is seen as
foreign, RA specific antibodies are produced
against this peptide, as…
Dendritic cells take up the the citrullinated
proteins (DR4) and present to the T cells
T cells activate a complementary B cell, which
becomes a plasma cell producing antibodies,
which is highly specific to the modified peptide
Lots of these antibodies are produced, so there
is immune complex formation, a macrophage or
neutrophil will come and try to engulf that.
Frustrated phagocytosis occurs, thus a releases
of a lot of the systemic components from those
macrophages into the inflammatory
environment, thus more neutrophil recruitment
and activation, so the cycle happens again and
again in a self sustaining inflammatory cycle, in
which the body tries to destroy the synovial
membrane
What is rheumatoid arthritis?
“arthro” – joint, “itis" – inflammation Risk factors
Autoimmune disease – inflammation Environmental
and destruction -Smoking
Commonest inflammatory joint -Obesity
disease – 1% population Genetic
Age of onset commonly 3rd to 6th -HLA DR4+
decade Immune response
3 times more prevalent in females -RF / anti-CCP positive (hallmark)
7 million sufferers by 2030 Moderate alcohol consumption may be beneficial in
Its symmetrical, if you have preventing onset –anti-inflammatory
defamation in one hand, you’re likely Excessive consumption – gout – inflammatory arthritis
to see the same in the other hand
All immune cells start as Haematopoietetic stem cells
These differentiate to become myeloid or lymphoid cells
IF goes down the Myeloid route typically innate immune system.
Innate immune system, is the first line of deffence, system responds the same way to each challenge it
encounters, responsiple for red blood cell and platlet production
More importantly prdocues: neutrophil, monocytes- macrophages and dendritic cells
Neutrophils and macrophages are phagocytes, so will engulf pathogens, removes debris and aim to restore
homeostasis
Dendritic cells are antigen presenting cells, so will take components from either the body, or outside the
body and will present them on their surface and provides the link to the adaptive immune system.
The dendritic cells present to T cells and B cells, which are produced by lymphoid progenitors
B cells produce antibpodies, t cells carry out effective functions: CD4= helper T cells (communicate with
other components of the immune system, so the components know when to activate, where to go ect),
CD8= cytotoxic T cells, which kill pathogens ( CD8 don’t play a huge role in rheumatoid arthritis)
, Diagnosis Rheumatoid factor (RF)
Antibodies that are raised against the crystalised fragments of
Joint Involvement- how many IgG (IgG is the most common form of antibody in the body in
are affected, sre they large general)
joints/ small joints Rheumatoid factors recognise the Anti-Fc region of IgG
Serology- positive for So you are producing antibodies in your body against IgG,
antibodies, such as rheumatoid which is problematic due to the prevalence of IgG in the body
factors and anti- CCP (one of The RF can be any class of antibodies: (in order of most
the main ways for diagnosis- if prevalent form: IgM > IgG > IgA > IgD > IgE
you have these antibodies it is So IgM and IgG are the main activators of the complement
likely RA) system contributes to the inflammatory affect
Acute phase reactants- proteins 80-85% of patients with RA become RF positive within 2
that are largely produced by years. so you can be RF negative for several months of having
liver, which are upregulated RA
with rheumatoid arthritis High titres of RF correlate with poor prognosis, so high levels
Duration- how long you’ve of RF= more likely for RA to be severe and progress faster
suffered with it Activation of complement system
Anti-cyclic citrullinated peptide (ANTI-CCP)
IgG antibody, which is produced against
synovial membrane peptides
These peptides are not normally exposed
However, when the joint starts to become
damaged, these peptides become exposed and
there is a change in arginine to a citrulline
These modified peptides are seen as foreign to
the body body acts against it
Only about 65% of RA patients have Anti-
CCP, but 95% of those with anti-CCP have RA
Diagnostic (because of the specificity(95%)
and prognostic, as high titres correlate with
disease severity
In RA: inflammation, destruction and
expansion of synovium
Granulocytes produce PAD
Action of PAD enzyme: converts arginine into
citrulline, so the modified peptide is seen as
foreign, RA specific antibodies are produced
against this peptide, as…
Dendritic cells take up the the citrullinated
proteins (DR4) and present to the T cells
T cells activate a complementary B cell, which
becomes a plasma cell producing antibodies,
which is highly specific to the modified peptide
Lots of these antibodies are produced, so there
is immune complex formation, a macrophage or
neutrophil will come and try to engulf that.
Frustrated phagocytosis occurs, thus a releases
of a lot of the systemic components from those
macrophages into the inflammatory
environment, thus more neutrophil recruitment
and activation, so the cycle happens again and
again in a self sustaining inflammatory cycle, in
which the body tries to destroy the synovial
membrane
